LE1 – Introduction
What are viruses?
- Small infectious agents with acellular organization
- Only reproduce within living cells (obligate intracellular parasites)
- Possess one type of nucleic acid for the genome, either DNA or RNA protected by a protein coat.
- Vehicle of transmission: virion. They have two conformations inside the virion and inside the
host cells.
Viruses are small: virion size 10-400 nm too small to be seen by light microscopy; you need electron
microscopy to see them although there are some of them that are giant so they can be seen by light
microscopy. There are a variety in sizes and shapes but similarities in morphology of viral particles which
are spherical or filamentous. Some viruses are naked while others are enveloped.
Virus coats
- Most of the viruses appear
- Genetic economy so they cannot have many different proteins to build the capsule so they
repeat few proteins.
- (nucleo)capsids/cores comprised of multiple copies (≥ 60) of a limited number of viral proteins
- subunits engage in regular, repetitive non-covalent interactions: symmetry
There are different symmetries:
- Helical structure
- Icosahedral structure
- Complex core structure:
- Pox virus
- HIV
Virus classification
- Host: very poor taxonomic criteria. They can jump into new species.
- Genome
- Monoploid just one genome or Diploid (in retroviruses) two molecules of the genome.
- Single or double stranded
- Linear or circular
- DNA or RNA
- Morphology
- Naked
- Enveloped
- Baltimore classification:
The Baltimore classification assigns viruses to seven
(I to VII) distinct classes on the basis of the nature
and polarity of their genomes. Because all viruses
must produce mRNA that can be translated by the
, cellular ribosome. These are the pathways required to produce mRNA, indicated by arrows.
Replication in eukaryotic cells:
- Main goal multiplication.
- The viral genome contains all the information to initiate and complete the viral cycle inside
the host cell.
Viral life cycle
- Attachment: Virus binds to host proteins on the surface.
- Penetration
- Uncoating
- Replication
- Transcription translation
- Assembly
- Release
Entry
- Attachment
- Penetration
- Uncoating
To deliver the genetic material into the host cell.
Entry requires breaching of the plasma membrane in order to introduce the viral genome in the
cytoplasm.
- Virions equipped with metastable proteins.
- Enveloped viruses: fusion proteins
- Naked viruses: pore-forming proteins
- Membrane fusion/pore formation requires conformational changes in virion(proteins)
- Triggered by appropriate cues.
- They end up getting into an endosome and they escape delivering their genetic material in the
perinuclear region.
- Transport along microtubules network
- Delivery of virions in endosomes and subviral particles
- Deep in the interior of the cell, in the perinuclear region
- Optimal site for virus replication
- Escape from endosome
- Low pH-triggering and/or cleavage of fusion proteins
Translation
DNA viruses
The host genetic system is based on DNA, so viral genome replication and expression could simply
emulate the host system. While the replication of viral and cellular DNA genomes is fundamentally
similar, the mechanistic details are varied because viral genomes are structurally diverse.
- Most DNA viruses replicate in the nucleus exception: poxviruses (cytoplasm)
, - Most DNA viruses possess a double stranded genome exception: parvovirus (linear single strand)
RNA viruses
Cells have no RNAdependent RNA polymerases that can replicate the genomes of RNA viruses or make
mRNA from RNA templates. One solution to this problem is that RNA virus genomes encode RNA
dependent RNA polymerases that produce RNA from RNA templates. The other solution is retrovirus,
which has reverse transcription of the genome to dsDNA, which can be transcribed by host RNA
polymerase.
● Most RNA viruses replicate in the cytoplasm except influenza virus (nucleus)
● Most RNA viruses possess a ss genome exception:
○ rotavirus (dsRNA)
○ retrovirus (diploid)
Genome polarity
Positive strand viruses: genome is mRNA sense: can be translated straight away into proteins which is
considered an infectious genome.
- Negative strand viruses: genome is anti-sense: cannot be translated genome so they are
non-infectious genomes and they must carry the RNAdependt-RNApolymerase in the virion
- Ambisense genome: contains genes in both orientations
Viral genes
Two types of proteins:
- Structural:structural proteins end up in the virion
- Non-structural proteins: replication enzymes and accessory proteins.
Viral genes are expressed to produce either:
- Individual proteins (1 mRNA, 1 protein)
- Polyproteins
After processing by viral and/or host proteinases.
, LE2 – Virus structure
Virions have 2 main functions: protect the genome from external threats and to transmit. In the
environment, things change in terms of pH, temperature, UV b, and enzymatic degradation. These
virions also need to find another host cell to infect. The virus particle has to be stable to protect from
environmental factors but at the same time can be disassembled for uncoating. This is mediated by
being in a metastable state (1), meaning that even though
the structure is stable, it has not reached the lowest possible
minimum energy. In order to get there, it needs to pass an
energy barrier (2) to allow refolding, which is triggered by
environmental cues such as receptor binding, pH, and
protease cleavage. After uncoating, the virion then reaches
the lowest possible energy state (3). In other words, the viral
structure resembles a spring loaded structure. It is stable at
a low energy, but it can still go to the lowest energy level upon the right trigger.
Function of virion proteins
1. Protection of the genome
- Assembly of a stable protective protein shell
- Specific recognition and packaging of the nucleic acid genome
- Interaction with host cell membranes to form the envelope
2. Delivery of the genome
- Binding to external receptors of the host cell
- Transmission of signals that induce uncoating of the genome
- Induction of fusion with host cell membranes
- Interaction with internal components of the infected cell to direct transport of the genome to
the appropriate site
3. Other functions
- Interactions with cellular components for transport to intracellular sites of assembly
- Interactions with cellular components to ensure an efficient infectious cycle
Terminologies
Subunit : Single, folded polypeptide chain
Structural unit (asymmetric unit): Unit from which capsids or nucleocapsids are built; may
comprise one protein subunit or multiple, different protein
subunits
Capsid (coat): The protein shell surrounding the nucleic acid genome
Nucleocapsid (core): The nucleic acid-protein assembly packaged within the virion;
used when this assembly is a discrete substructure of a particle
Envelope (viral membrane): The host cell-derived lipid bilayer carrying viral glycoproteins
Virion: The infectious virus particle
What are viruses?
- Small infectious agents with acellular organization
- Only reproduce within living cells (obligate intracellular parasites)
- Possess one type of nucleic acid for the genome, either DNA or RNA protected by a protein coat.
- Vehicle of transmission: virion. They have two conformations inside the virion and inside the
host cells.
Viruses are small: virion size 10-400 nm too small to be seen by light microscopy; you need electron
microscopy to see them although there are some of them that are giant so they can be seen by light
microscopy. There are a variety in sizes and shapes but similarities in morphology of viral particles which
are spherical or filamentous. Some viruses are naked while others are enveloped.
Virus coats
- Most of the viruses appear
- Genetic economy so they cannot have many different proteins to build the capsule so they
repeat few proteins.
- (nucleo)capsids/cores comprised of multiple copies (≥ 60) of a limited number of viral proteins
- subunits engage in regular, repetitive non-covalent interactions: symmetry
There are different symmetries:
- Helical structure
- Icosahedral structure
- Complex core structure:
- Pox virus
- HIV
Virus classification
- Host: very poor taxonomic criteria. They can jump into new species.
- Genome
- Monoploid just one genome or Diploid (in retroviruses) two molecules of the genome.
- Single or double stranded
- Linear or circular
- DNA or RNA
- Morphology
- Naked
- Enveloped
- Baltimore classification:
The Baltimore classification assigns viruses to seven
(I to VII) distinct classes on the basis of the nature
and polarity of their genomes. Because all viruses
must produce mRNA that can be translated by the
, cellular ribosome. These are the pathways required to produce mRNA, indicated by arrows.
Replication in eukaryotic cells:
- Main goal multiplication.
- The viral genome contains all the information to initiate and complete the viral cycle inside
the host cell.
Viral life cycle
- Attachment: Virus binds to host proteins on the surface.
- Penetration
- Uncoating
- Replication
- Transcription translation
- Assembly
- Release
Entry
- Attachment
- Penetration
- Uncoating
To deliver the genetic material into the host cell.
Entry requires breaching of the plasma membrane in order to introduce the viral genome in the
cytoplasm.
- Virions equipped with metastable proteins.
- Enveloped viruses: fusion proteins
- Naked viruses: pore-forming proteins
- Membrane fusion/pore formation requires conformational changes in virion(proteins)
- Triggered by appropriate cues.
- They end up getting into an endosome and they escape delivering their genetic material in the
perinuclear region.
- Transport along microtubules network
- Delivery of virions in endosomes and subviral particles
- Deep in the interior of the cell, in the perinuclear region
- Optimal site for virus replication
- Escape from endosome
- Low pH-triggering and/or cleavage of fusion proteins
Translation
DNA viruses
The host genetic system is based on DNA, so viral genome replication and expression could simply
emulate the host system. While the replication of viral and cellular DNA genomes is fundamentally
similar, the mechanistic details are varied because viral genomes are structurally diverse.
- Most DNA viruses replicate in the nucleus exception: poxviruses (cytoplasm)
, - Most DNA viruses possess a double stranded genome exception: parvovirus (linear single strand)
RNA viruses
Cells have no RNAdependent RNA polymerases that can replicate the genomes of RNA viruses or make
mRNA from RNA templates. One solution to this problem is that RNA virus genomes encode RNA
dependent RNA polymerases that produce RNA from RNA templates. The other solution is retrovirus,
which has reverse transcription of the genome to dsDNA, which can be transcribed by host RNA
polymerase.
● Most RNA viruses replicate in the cytoplasm except influenza virus (nucleus)
● Most RNA viruses possess a ss genome exception:
○ rotavirus (dsRNA)
○ retrovirus (diploid)
Genome polarity
Positive strand viruses: genome is mRNA sense: can be translated straight away into proteins which is
considered an infectious genome.
- Negative strand viruses: genome is anti-sense: cannot be translated genome so they are
non-infectious genomes and they must carry the RNAdependt-RNApolymerase in the virion
- Ambisense genome: contains genes in both orientations
Viral genes
Two types of proteins:
- Structural:structural proteins end up in the virion
- Non-structural proteins: replication enzymes and accessory proteins.
Viral genes are expressed to produce either:
- Individual proteins (1 mRNA, 1 protein)
- Polyproteins
After processing by viral and/or host proteinases.
, LE2 – Virus structure
Virions have 2 main functions: protect the genome from external threats and to transmit. In the
environment, things change in terms of pH, temperature, UV b, and enzymatic degradation. These
virions also need to find another host cell to infect. The virus particle has to be stable to protect from
environmental factors but at the same time can be disassembled for uncoating. This is mediated by
being in a metastable state (1), meaning that even though
the structure is stable, it has not reached the lowest possible
minimum energy. In order to get there, it needs to pass an
energy barrier (2) to allow refolding, which is triggered by
environmental cues such as receptor binding, pH, and
protease cleavage. After uncoating, the virion then reaches
the lowest possible energy state (3). In other words, the viral
structure resembles a spring loaded structure. It is stable at
a low energy, but it can still go to the lowest energy level upon the right trigger.
Function of virion proteins
1. Protection of the genome
- Assembly of a stable protective protein shell
- Specific recognition and packaging of the nucleic acid genome
- Interaction with host cell membranes to form the envelope
2. Delivery of the genome
- Binding to external receptors of the host cell
- Transmission of signals that induce uncoating of the genome
- Induction of fusion with host cell membranes
- Interaction with internal components of the infected cell to direct transport of the genome to
the appropriate site
3. Other functions
- Interactions with cellular components for transport to intracellular sites of assembly
- Interactions with cellular components to ensure an efficient infectious cycle
Terminologies
Subunit : Single, folded polypeptide chain
Structural unit (asymmetric unit): Unit from which capsids or nucleocapsids are built; may
comprise one protein subunit or multiple, different protein
subunits
Capsid (coat): The protein shell surrounding the nucleic acid genome
Nucleocapsid (core): The nucleic acid-protein assembly packaged within the virion;
used when this assembly is a discrete substructure of a particle
Envelope (viral membrane): The host cell-derived lipid bilayer carrying viral glycoproteins
Virion: The infectious virus particle
